Smad3 binds scleraxis and mohawk and regulates tendon matrix organization

TGF plays a critical role in tendon formation and healing. While its downstream effector Smad3 has been implicated in the healing process, little is known about the role of Smad3 in normal tendon development or tenocyte gene expression. Using mice deficient in Smad3 (Smad3(-/-)), we show that Smad3 ablation disrupts tendon architecture and has a dramatic impact on normal gene and protein expression during development as well as in mature tendon. In developing and adult tendon, loss of Smad3 results in reduced protein expression of the matrix components Collagen 1 and Tenascin-C. Additionally, when compared to wild type, tendon from adult Smad3(-/-) mice shows a down regulation of key tendon marker genes. Finally, we have established that Smad3 has the ability to physically interact with the critical transcriptional regulators Scleraxis and Mohawk. Together these results indicate a central role for Smad3 in normal tendon formation and in the maintenance of mature tendon. (c) 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1475-1483, 2013